The present invention is directed to a novel process for preparing arylpiperazinyl-ethyl(or butyl)-heterocyclic compounds and their pharmaceutically acceptable acid addition salts.
U.S. Pat. No. 4,831,031, the disclosure of which is hereby incorporated herein by reference, indicates that arylpiperazinyl-ethyl(or butyl)-heterocyclic compounds may be prepared by reacting piperazines of the formula II with compounds of the formula III as follows: ##STR4## Wherein Hal is fluoro, chloro, bromo or iodo; and Ar, n, X and Y are as defined therein with reference to formula I. The '031 patent indicates that this coupling reaction is generally conducted in a polar solvent, such as a lower alcohol, dimethylformamide or methylisobutylketone, and in the presence of a weak base and that, preferably, the reaction is in the further presence of a catalytic amount of sodium iodide, and a neutralizing agent for hydrochloride such as sodium carbonate.
The present invention relates to a new and useful process for effecting coupling reactions of piperazine derivatives with alkyl halide derivatives that provide aryl piperazinyl-ethyl (or butyl)-heterocyclic compounds in greater yields than known methods. In the present invention, the coupling reaction is conducted in water. This aqueous process has not shown formation of byproducts in contrast to previous methods which produce undesirable byproducts and require special isolation procedures, i.e., extractions, distillations and recrystallizations.